The present invention concerns an apparatus and a solution for removing aluminum ions from blood. For more than 20 years it has been known that aluminum is deposited in the bones of dialysis patients and that it is therefore necessary to keep aluminum away from the bodies of such patients or to remove it therefrom.
In healthy persons aluminum is excreted almost exclusively through the kidneys. Patients lacking their own kidney function cannot perform this excretion. They accumulate the aluminum in the body if the intake of aluminum exceeds the excretion carried out by means of the dialysis treatment conventionally performed three times per week.
The main sources of aluminum intake are aluminum hydroxide based phosphate binders, drinking water, food prepared or stored in aluminum receptacles and a range of pharmaceuticals.
The excretion of aluminum through the membrane of a dialyzer during dialysis is usually relatively minimal. Thus, even in modern open-pore high-flux dialyzers a reduction of only 40% of the aluminum level is achieved during passage through the dialyzer. The remaining aluminum therefore settles in the bones, causing bone cysts and osteomalacia. Since, after 5 years of dialysis treatment, almost every patient displays more or less significant aluminum deposits in bones and tissue, this results in considerable deterioration of the general health of the patient.
From the DE-OS 40 04 978 it is known to eliminate aluminum ions from the organism in the context of preventive Morbus Alzheimer therapy. This may be achieved by peroral administration of synthetic complexing agents, in particular of hydroxyaromates comprising protective groups. The affinity of the complexing agents with aluminum ions is thereby greater than that of citrate or ATP.
However, major side-effects may occur due to the oral administration of the complexing agents and the systemic effects caused thereby.
Experiments have further already been conducted (Humpfner, A., "Aluminiumtoxikation bei Niereninsuffizienz", Zuckschwerdt Verlag, Munich 1989) with the object of improving the purification performance of dialyzers with the aid of chelate generators, e.g. desferrioxamine (DFO). Such chelate generators were either administered orally, thus also producing systemic effects, or they were applied with a perfusor, or they were applied intramuscularly (i.m.), slowly intravenously (i.v.), subcutaneously, or also intraperitoneally.
Although good initial results were obtained by the administration of DFO, it was not possible to perform chronic treatment with this method, since DFO proved to be too toxic. It was thus impossible to remove the ingested aluminum directly, i.e. during the next dialysis treatment. It therefore became practice to administer DFO only in certain intervals in the form of cures, during which the aluminum in the bones was mobilized and subsequently removed with the aid of dialysis. The disadvantage of such treatments is that a relatively high concentration of aluminum in the bones must first be achieved and that, during the interval between the administration of DFO and the removal of the A1-DFO complex by means of dialysis (usually on the following day), significant concentrations of aluminum (predominantly in the form of DFO complex) occur in the blood, causing massive side-effects.
As early as 1961, Manira et al. (Am. J. Med. Sci., 242, pp. 32 ff.) already reported experiments concerning the use of tri-sodium citrate for regional anti-coagulation in dialysis treatment.
Avoiding the use of heparin as an anti-coagulant, tri-sodium citrate was introduced into the bloodstream by means of infusion immediately prior to the flow through the dialyzer.
Since no heparin is used at all, this method requires the administration of high doses of tri-sodium citrate to prevent a possible activation of the coagulation system on the foreign surface of the conduction system of the extra-corporeal bloodstream and thus ensure safe anti-coagulation.
With the high flow rates of 200-300 ml/min conventionally obtained today, this results in a high level of citrate being introduced into the body of the patient. This may be balanced by intravenous administration of calcium, which, however, represents process-technological problems.
In addition, an excessive introduction of tri-sodium citrate into the blood may result in an undesirable rise of the blood sodium level causing high blood pressure.
The use of citrate during dialysis treatment therefore appeared unadvisable.
In the WO 91/06326 the replacement of heparin by citrate was again dealt with, whereby citrate was introduced into the blood circulation as an anticoagulant, downstream from the dialyzer. To prevent alkaloses resulting from the decomposition of citric acid into CO.sub.2 and H.sub.2 O in the course of metabolism, complex additional measures were employed in the process described in the WO. A dialyzate having sodium and calcium concentrations below the normal levels wag, inter alia, used, as well as a total alkali concentration sufficient to protect against alkaloses.